The major purpose of this study is to evaluate the immediate and long term results of intensive antituberculosis chemotherapy in the treatment of isoniazid-resistant mycobacterial infections. The intensive chemotherapy regimens are selected on the basis of drug susceptibility studies, whenever possible. Multiple antituberculosis drugs are necessary in all cases. Generally, three drugs are used in combination; but with highly resistant organisms, five or six drugs may be necessary for successful treatment. More than 900 patients have been included in this study since its beginning which is restricted to those with cultures positive for mycobacteria with isoniazid resistance. The majority of the patients represent therapy failures on conventional antituberculosis drug regimens and are major therapeutic challenges. Included in this study are patients with atypical mycobacterial infections. These mycobacteria are characterized by natural isoniazid resistance. Followup studies are in progress on all patients treated with these intensive regimens in order to assess the immediate and the long term chemotherapy results and to evaluate long-term drug toxicities. Rifampin is the most recently included drug in these studies and has been highly effective in treating patients with isoniazid resistant M. tuberculosis and M. kansasii infections. Unfortunately, rifampin has been used in less than optimum circumstances in some patients before admission to this study so that the majority are now resistant to this drug. As a consequence, treatment and evaluation have become more complex; and new approaches are necessary including immunological studies and unusual drug combinations. This study also includes an analysis of the behavior of each drug used in terms of efficacy, toxicity, and adverse reactions. This series is one of the largest retreatment experiences available and therefore provides essential information concerning the problems associated with intensive antituberculosis chemotherapy.